Molecular mechanisms associated with oxidative damage in the mouse testis induced by LaCl₃

Area of Science:

• Toxicology
• Environmental Health
• Reproductive Biology

Background:

• Rare earth elements, particularly lanthanum chloride (LaCl3), are globally significant due to China's production dominance.
• Previous research indicates potential for rare earth elements to induce oxidative damage in animal testes.
• The precise molecular mechanisms of LaCl3-induced testicular toxicity remain incompletely understood.

Purpose of the Study:

• To investigate the regulatory role of the nuclear factor erythroid-2 related factor 2 (Nrf-2)/antioxidant response element (ARE) pathway in LaCl3-induced testicular oxidative stress.
• To elucidate the molecular mechanisms underlying LaCl3 toxicity in the male mouse reproductive system.

Main Methods:

• Male mice were administered varying doses of LaCl3 (10, 20, 40 mg/kg body weight) daily for 90 days.
• Evaluated testicular pathological changes, apoptosis, lipid, protein, and DNA peroxidation.
• Assessed reactive oxygen species (ROS) levels, antioxidant enzyme activities (SOD, GSH-Px, GST), glutathione (GSH) content, and the expression of key proteins in the Nrf-2/ARE pathway.

Main Results:

• LaCl3 exposure induced significant testicular pathology and apoptosis in spermatogenic cells.
• Increased lipid, protein, and DNA peroxidation, elevated ROS production, and reduced antioxidant enzyme activities and GSH content were observed.
• LaCl3 exposure downregulated Nrf-2 and its downstream targets (HO-1, GCLC, NQO1, PKC, PI3K) while upregulating Keap1 expression.

Conclusions:

• LaCl3-induced testicular oxidative damage in male mice is associated with the inhibition of the Nrf-2/ARE pathway activation.
• The findings highlight the critical role of the Nrf-2/ARE pathway in mitigating LaCl3-induced testicular toxicity.
• This study provides crucial insights into the molecular mechanisms of rare earth element toxicity on male reproductive health.